Comparison of three regimens for treatment of mild to moderate Pneumocystis carinii pneumonia in patients with AIDS: A double-blind, randomized trial of oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine

Sharon Safrin, Dianne M. Finkelstein, Judith Feinberg, Peter Frame, Gail Simpson, Albert W Wu, Tony Cheung, Ruy Soeiro, Peter Hojczyk, John R. Black

Research output: Contribution to journalArticle

Abstract

Objective: To compare the tolerability and efficacy of three oral regimens for the treatment of patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia. Design: A randomized, double-blind study. Setting: 24 U.S. academic medical centers. Patients: 181 patients with morphologically confirmed P. carinii pneumonia and alveolar-arterial oxygen differences (PAO2-PaO2) of 45 mm Hg or less. Intervention: Patients were randomly assigned to receive trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for 21 days. Patients with a PAO2-PaO2 of 35 to 45 mm Hg at study entry also received prednisone. Measurements: Serial clinical and laboratory evaluations for therapeutic response and toxicity. Therapeutic failure at day 21 was defined by any of the following: increase in PAO2-PaO2 of greater than 20 mm Hg; no remission of baseline signs and symptoms; and change in antipneumocystis therapy for reasons other than toxicity, intubation, or death. Dose-limiting toxicity was defined as discontinuation of therapy by the primary physician because of one or more adverse reactions. Results: No statistically significant differences were seen among treatment groups in the proportions of patients who had dose-limiting toxicity (P = 0.2), therapeutic failure (P > 0.2), or a complete course of therapy (P > 0.2). Survival during therapy or for 2 months thereafter did not differ among the three groups (P > 0.2). However, elevation of serum aminotransferase levels to more than five times the baseline levels was more frequent in the trimethoprim-sulfamethoxazole group (P - 0.003), and one or more serious hematologic toxicities (neutropenia, anemia, thrombocytopenia, or methemoglobinemia) occurred more frequently in the clindamycin-primaquine group (P = 0.01). Conclusions: The rates of dose-limiting toxicity, therapeutic failure, and survival did not differ among patients with AIDS who were receiving oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for mild to moderate P. carinii pneumonia. However, the limited sample size prevents the unequivocal demonstration of the equality of these three regimens. Differences in expected categories of toxicities associated with each regimen should guide the clinician in choosing first-line therapy, particularly for patients with baseline hepatic insufficiency or myelosuppression.

Original languageEnglish (US)
Pages (from-to)792-802
Number of pages11
JournalAnnals of Internal Medicine
Volume124
Issue number9
StatePublished - May 1 1996

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Primaquine
Dapsone
Trimethoprim
Pneumocystis Pneumonia
Clindamycin
Sulfamethoxazole Drug Combination Trimethoprim
Acquired Immunodeficiency Syndrome
Therapeutics
Hepatic Insufficiency
Methemoglobinemia
Survival
Prednisone
Transaminases
Neutropenia
Double-Blind Method
Intubation
Thrombocytopenia
Sample Size
Signs and Symptoms
Anemia

ASJC Scopus subject areas

  • Medicine(all)

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Comparison of three regimens for treatment of mild to moderate Pneumocystis carinii pneumonia in patients with AIDS : A double-blind, randomized trial of oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine. / Safrin, Sharon; Finkelstein, Dianne M.; Feinberg, Judith; Frame, Peter; Simpson, Gail; Wu, Albert W; Cheung, Tony; Soeiro, Ruy; Hojczyk, Peter; Black, John R.

In: Annals of Internal Medicine, Vol. 124, No. 9, 01.05.1996, p. 792-802.

Research output: Contribution to journalArticle

Safrin, Sharon ; Finkelstein, Dianne M. ; Feinberg, Judith ; Frame, Peter ; Simpson, Gail ; Wu, Albert W ; Cheung, Tony ; Soeiro, Ruy ; Hojczyk, Peter ; Black, John R. / Comparison of three regimens for treatment of mild to moderate Pneumocystis carinii pneumonia in patients with AIDS : A double-blind, randomized trial of oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine. In: Annals of Internal Medicine. 1996 ; Vol. 124, No. 9. pp. 792-802.
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abstract = "Objective: To compare the tolerability and efficacy of three oral regimens for the treatment of patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia. Design: A randomized, double-blind study. Setting: 24 U.S. academic medical centers. Patients: 181 patients with morphologically confirmed P. carinii pneumonia and alveolar-arterial oxygen differences (PAO2-PaO2) of 45 mm Hg or less. Intervention: Patients were randomly assigned to receive trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for 21 days. Patients with a PAO2-PaO2 of 35 to 45 mm Hg at study entry also received prednisone. Measurements: Serial clinical and laboratory evaluations for therapeutic response and toxicity. Therapeutic failure at day 21 was defined by any of the following: increase in PAO2-PaO2 of greater than 20 mm Hg; no remission of baseline signs and symptoms; and change in antipneumocystis therapy for reasons other than toxicity, intubation, or death. Dose-limiting toxicity was defined as discontinuation of therapy by the primary physician because of one or more adverse reactions. Results: No statistically significant differences were seen among treatment groups in the proportions of patients who had dose-limiting toxicity (P = 0.2), therapeutic failure (P > 0.2), or a complete course of therapy (P > 0.2). Survival during therapy or for 2 months thereafter did not differ among the three groups (P > 0.2). However, elevation of serum aminotransferase levels to more than five times the baseline levels was more frequent in the trimethoprim-sulfamethoxazole group (P - 0.003), and one or more serious hematologic toxicities (neutropenia, anemia, thrombocytopenia, or methemoglobinemia) occurred more frequently in the clindamycin-primaquine group (P = 0.01). Conclusions: The rates of dose-limiting toxicity, therapeutic failure, and survival did not differ among patients with AIDS who were receiving oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for mild to moderate P. carinii pneumonia. However, the limited sample size prevents the unequivocal demonstration of the equality of these three regimens. Differences in expected categories of toxicities associated with each regimen should guide the clinician in choosing first-line therapy, particularly for patients with baseline hepatic insufficiency or myelosuppression.",
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T1 - Comparison of three regimens for treatment of mild to moderate Pneumocystis carinii pneumonia in patients with AIDS

T2 - A double-blind, randomized trial of oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine

AU - Safrin, Sharon

AU - Finkelstein, Dianne M.

AU - Feinberg, Judith

AU - Frame, Peter

AU - Simpson, Gail

AU - Wu, Albert W

AU - Cheung, Tony

AU - Soeiro, Ruy

AU - Hojczyk, Peter

AU - Black, John R.

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N2 - Objective: To compare the tolerability and efficacy of three oral regimens for the treatment of patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia. Design: A randomized, double-blind study. Setting: 24 U.S. academic medical centers. Patients: 181 patients with morphologically confirmed P. carinii pneumonia and alveolar-arterial oxygen differences (PAO2-PaO2) of 45 mm Hg or less. Intervention: Patients were randomly assigned to receive trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for 21 days. Patients with a PAO2-PaO2 of 35 to 45 mm Hg at study entry also received prednisone. Measurements: Serial clinical and laboratory evaluations for therapeutic response and toxicity. Therapeutic failure at day 21 was defined by any of the following: increase in PAO2-PaO2 of greater than 20 mm Hg; no remission of baseline signs and symptoms; and change in antipneumocystis therapy for reasons other than toxicity, intubation, or death. Dose-limiting toxicity was defined as discontinuation of therapy by the primary physician because of one or more adverse reactions. Results: No statistically significant differences were seen among treatment groups in the proportions of patients who had dose-limiting toxicity (P = 0.2), therapeutic failure (P > 0.2), or a complete course of therapy (P > 0.2). Survival during therapy or for 2 months thereafter did not differ among the three groups (P > 0.2). However, elevation of serum aminotransferase levels to more than five times the baseline levels was more frequent in the trimethoprim-sulfamethoxazole group (P - 0.003), and one or more serious hematologic toxicities (neutropenia, anemia, thrombocytopenia, or methemoglobinemia) occurred more frequently in the clindamycin-primaquine group (P = 0.01). Conclusions: The rates of dose-limiting toxicity, therapeutic failure, and survival did not differ among patients with AIDS who were receiving oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for mild to moderate P. carinii pneumonia. However, the limited sample size prevents the unequivocal demonstration of the equality of these three regimens. Differences in expected categories of toxicities associated with each regimen should guide the clinician in choosing first-line therapy, particularly for patients with baseline hepatic insufficiency or myelosuppression.

AB - Objective: To compare the tolerability and efficacy of three oral regimens for the treatment of patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia. Design: A randomized, double-blind study. Setting: 24 U.S. academic medical centers. Patients: 181 patients with morphologically confirmed P. carinii pneumonia and alveolar-arterial oxygen differences (PAO2-PaO2) of 45 mm Hg or less. Intervention: Patients were randomly assigned to receive trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for 21 days. Patients with a PAO2-PaO2 of 35 to 45 mm Hg at study entry also received prednisone. Measurements: Serial clinical and laboratory evaluations for therapeutic response and toxicity. Therapeutic failure at day 21 was defined by any of the following: increase in PAO2-PaO2 of greater than 20 mm Hg; no remission of baseline signs and symptoms; and change in antipneumocystis therapy for reasons other than toxicity, intubation, or death. Dose-limiting toxicity was defined as discontinuation of therapy by the primary physician because of one or more adverse reactions. Results: No statistically significant differences were seen among treatment groups in the proportions of patients who had dose-limiting toxicity (P = 0.2), therapeutic failure (P > 0.2), or a complete course of therapy (P > 0.2). Survival during therapy or for 2 months thereafter did not differ among the three groups (P > 0.2). However, elevation of serum aminotransferase levels to more than five times the baseline levels was more frequent in the trimethoprim-sulfamethoxazole group (P - 0.003), and one or more serious hematologic toxicities (neutropenia, anemia, thrombocytopenia, or methemoglobinemia) occurred more frequently in the clindamycin-primaquine group (P = 0.01). Conclusions: The rates of dose-limiting toxicity, therapeutic failure, and survival did not differ among patients with AIDS who were receiving oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for mild to moderate P. carinii pneumonia. However, the limited sample size prevents the unequivocal demonstration of the equality of these three regimens. Differences in expected categories of toxicities associated with each regimen should guide the clinician in choosing first-line therapy, particularly for patients with baseline hepatic insufficiency or myelosuppression.

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